These studies define the biochemical mechanisms whereby age-dependent changes in regulation of intermediary metabolism perturb physiological control systems and, thus, lead to a failure to maintain homeostasis in the aged. Investigation include: 1) regulation of carbohydrate and fat oxidation; 2) mechanism of control of puruvate dehydrogenase activity, 3) loci of the deficits in mitochondrial oxidations in aged animals; 4) the role of Ca2 ions in regulating the activity of bioenergetic reactions.